Research progress of irisin in acute kidney injury_West China Medical Journal

Authors：

CHEN Ting ^1,2 ,  HUANG Wenhui ² , XU Lili ^1,2 , CHEN Caihe ^1,2

1. The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P. R. China;
2. Department of Nephrology, Gansu People’s Hospital, Lanzhou, Gansu 730000, P. R. China;

Corresponding author：

HUANG Wenhui, Email: huangwh@163.com

Keywords：

Irisin; acute kidney injury; ischemia/reperfusion; sepsis

DOI：

10.7507/1002-0179.202208078

Video：

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Acute kidney injury (AKI) is a systemic inflammatory disease with limited treatment options. Irisin is a novel actin protein produced by skeletal muscle movement and exerts anti-inflammatory, anti-apoptotic, and antioxidant effects by participating in multiple signaling pathways. In recent years, the protective effect of irisin on AKI has attracted much attention, and its regulatory mechanism involves a complex network of signaling pathways, which can reduce oxidative stress, inhibit apoptosis, inhibit inflammation, and inhibit ferroptosis under pathological conditions. This pathway alleviates kidney injury by enhancing the metabolic reprogramming of tubular cells while attenuating fibrosis. Irisin is expected to be a new treatment option for AKI.

Citation： CHEN Ting, HUANG Wenhui, XU Lili, CHEN Caihe. Research progress of irisin in acute kidney injury. West China Medical Journal, 2023, 38(1): 116-120. doi: 10.7507/1002-0179.202208078 Copy

1.	Susantitaphong P, Cruz DN, Cerda J, et al. World incidence of AKI: a meta-analysis. Clin J Am Soc Nephrol, 2013, 8(9): 1482-1493.
2.	Chang YM, Chou YT, Kan WC, et al. Sepsis and acute kidney injury: a review focusing on the bidirectional interplay. Int J Mol Sci, 2022, 23(16): 9159.
3.	Ruas AFL, Lébeis GM, de Castro NB, et al. Acute kidney injury in pediatrics: an overview focusing on pathophysiology. Pediatr Nephrol, 2022, 37(9): 2037-2052.
4.	Guo C, Dong G, Liang X, et al. Epigenetic regulation in AKI and kidney repair: mechanisms and therapeutic implications. Nat Rev Nephrol, 2019, 15(4): 220-239.
5.	Dellepiane S, Marengo M, Cantaluppi V. Detrimental cross-talk between sepsis and acute kidney injury: new pathogenic mechanisms, early biomarkers and targeted therapies. Crit Care, 2016, 20: 61.
6.	Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012, 481(7382): 463-468.
7.	Waseem R, Shamsi A, Mohammad T, et al. FNDC5/irisin: physiology and pathophysiology. Molecules, 2022, 27(3): 1118.
8.	Liu Y, Fu Y, Liu Z, et al. Irisin is induced in renal ischemia-reperfusion to protect against tubular cell injury via suppressing p53. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(7): 165792.
9.	Jin YH, Li ZY, Jiang XQ, et al. Irisin alleviates renal injury caused by sepsis via the NF-κB signaling pathway. Eur Rev Med Pharmacol Sci, 2020, 24(11): 6470-6476.
10.	Shao L, Meng D, Yang F, et al. Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells. Biochem Biophys Res Commun, 2017, 487(2): 194-200.
11.	Tsuchiya Y, Ando D, Goto K, et al. High-intensity exercise causes greater irisin response compared with low-intensity exercise under similar energy consumption. Tohoku J Exp Med, 2014, 233(2): 135-140.
12.	Zhang Y, Li R, Meng Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes, 2014, 63(2): 514-525.
13.	Korta P, Pocheć E, Mazur-Biały A. Irisin as a multifunctional protein: implications for health and certain diseases. Medicina (Kaunas), 2019, 55(8): 485.
14.	Daudon M, Bigot Y, Dupont J, et al. Irisin and the fibronectin type Ⅲ domain-containing family: structure, signaling and role in female reproduction. Reproduction, 2022, 164(1): R1-R9.
15.	Zhao R. Irisin at the crossroads of inter-organ communications: challenge and implications. Front Endocrinol (Lausanne), 2022, 13: 989135.
16.	Matsuo Y, Gleitsmann K, Mangner N, et al. Fibronectin type Ⅲ domain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines. J Cachexia Sarcopenia Muscle, 2015, 6(1): 62-72.
17.	Kurdiova T, Balaz M, Vician M, et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol, 2014, 592(5): 1091-1107.
18.	Luo Y, Qiao X, Xu L, et al. Irisin: circulating levels in serum and its relation to gonadal axis. Endocrine, 2022, 75(3): 663-671.
19.	Lee HJ, Lee JO, Kim N, et al. Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK. Mol Endocrinol, 2015, 29(6): 873-881.
20.	Luna-Ceron E, González-Gil AM, Elizondo-Montemayor L. Current insights on the role of irisin in endothelial dysfunction. Curr Vasc Pharmacol, 2022, 20(3): 205-220.
21.	Zheng S, Chen N, Kang X, et al. Irisin alleviates FFA induced β-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway. Endocrine, 2022, 75(3): 740-751.
22.	毛楠, 周琬秋, 任思冲, 等. 鸢尾素与急性肾损伤的相关性研究. 成都医学院学报, 2022, 17(2): 174-179.
23.	Sadeghi Shad J, Akbari R, Qujeq D, et al. Measurement of serum irisin in the different stages of chronic kidney disease. Caspian J Intern Med, 2019, 10(3): 314-319.
24.	Csiky B, Sági B, Emmert V, et al. Cardiometabolic effects of irisin in patients with end-stage renal disease on regular hemo- or peritoneal dialysis. Blood Purif, 2022, 51(5): 450-457.
25.	邵雯, 李荣山, 周晓霜. 维持性血液透析合并肌少症患者血清鸢尾素的变化. 华西医学, 2020, 35(7): 788-793.
26.	Arcidiacono T, Magni G, Macrina L, et al. Serum irisin may predict cardiovascular events in elderly patients with chronic kidney disease stage 3-5. J Ren Nutr, 2022, 32(3): 282-291.
27.	Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev, 2015, 4(2): 20-27.
28.	Bi J, Yang L, Wang T, et al. Irisin improves autophagy of aged hepatocytes via increasing telomerase activity in liver injury. Oxid Med Cell Longev, 2020, 2020: 6946037.
29.	Zhang J, Bi J, Ren Y, et al. Involvement of GPX4 in irisin’s protection against ischemia reperfusion-induced acute kidney injury. J Cell Physiol, 2021, 236(2): 931-945.
30.	Qiongyue Z, Xin Y, Meng P, et al. Post-treatment with irisin attenuates acute kidney injury in sepsis mice through anti-ferroptosis via the SIRT1/Nrf2 pathway. Front Pharmacol, 2022, 13: 857067.
31.	Jin Z, Guo P, Li X, et al. Neuroprotective effects of irisin against cerebral ischemia/reperfusion injury via Notch signaling pathway. Biomed Pharmacother, 2019, 120: 109452.
32.	Zhang R, Ji J, Zhou X, et al. Irisin pretreatment protects kidneys against acute kidney injury induced by ischemia/reperfusion via upregulating the expression of uncoupling protein 2. Biomed Res Int, 2020, 2020: 6537371.
33.	Fan H, Su BJ, Le JW, et al. Salidroside protects acute kidney injury in septic rats by inhibiting inflammation and apoptosis. Drug Des Devel Ther, 2022, 16: 899-907.
34.	Baisantry A, Berkenkamp B, Rong S, et al. Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion. Am J Physiol Renal Physiol, 2019, 316(6): F1124-F1132.
35.	Friederich M, Fasching A, Hansell P, et al. Diabetes-induced up-regulation of uncoupling protein-2 results in increased mitochondrial uncoupling in kidney proximal tubular cells. Biochim Biophys Acta, 2008, 1777(7/8): 935-940.
36.	Zhou Y, Cai T, Xu J, et al. UCP2 attenuates apoptosis of tubular epithelial cells in renal ischemia-reperfusion injury. Am J Physiol Renal Physiol, 2017, 313(4): F926-F937.
37.	Gwon DH, Hwang TW, Ro JY, et al. High endogenous accumulation of ω-3 polyunsaturated fatty acids protect against ischemia-reperfusion renal injury through AMPK-mediated autophagy in fat-1 mice. Int J Mol Sci, 2017, 18(10): 2081.
38.	Formigari GP, Dátilo MN, Vareda B, et al. Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy. Sci Rep, 2022, 12(1): 9062.
39.	Zunner BEM, Wachsmuth NB, Eckstein ML, et al. Myokines and resistance training: a narrative review. Int J Mol Sci, 2022, 23(7): 3501.
40.	Wu F, Li Z, Cai M, et al. Aerobic exercise alleviates oxidative stress-induced apoptosis in kidneys of myocardial infarction mice by inhibiting ALCAT1 and activating FNDC5/irisin signaling pathway. Free Radic Biol Med. 2020, 158: 171-180.
41.	Ortega-Lozano AJ, Jiménez-Uribe AP, Aranda-Rivera AK, et al. Expression profiles of kidney mitochondrial proteome during the progression of the unilateral ureteral obstruction: focus on energy metabolism adaptions. Metabolites, 2022, 12(10): 936.
42.	Peng H, Wang Q, Lou T, et al. Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys. Nat Commun, 2017, 8(1): 1493.

1. Susantitaphong P, Cruz DN, Cerda J, et al. World incidence of AKI: a meta-analysis. Clin J Am Soc Nephrol, 2013, 8(9): 1482-1493.
2. Chang YM, Chou YT, Kan WC, et al. Sepsis and acute kidney injury: a review focusing on the bidirectional interplay. Int J Mol Sci, 2022, 23(16): 9159.
3. Ruas AFL, Lébeis GM, de Castro NB, et al. Acute kidney injury in pediatrics: an overview focusing on pathophysiology. Pediatr Nephrol, 2022, 37(9): 2037-2052.
4. Guo C, Dong G, Liang X, et al. Epigenetic regulation in AKI and kidney repair: mechanisms and therapeutic implications. Nat Rev Nephrol, 2019, 15(4): 220-239.
5. Dellepiane S, Marengo M, Cantaluppi V. Detrimental cross-talk between sepsis and acute kidney injury: new pathogenic mechanisms, early biomarkers and targeted therapies. Crit Care, 2016, 20: 61.
6. Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012, 481(7382): 463-468.
7. Waseem R, Shamsi A, Mohammad T, et al. FNDC5/irisin: physiology and pathophysiology. Molecules, 2022, 27(3): 1118.
8. Liu Y, Fu Y, Liu Z, et al. Irisin is induced in renal ischemia-reperfusion to protect against tubular cell injury via suppressing p53. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(7): 165792.
9. Jin YH, Li ZY, Jiang XQ, et al. Irisin alleviates renal injury caused by sepsis via the NF-κB signaling pathway. Eur Rev Med Pharmacol Sci, 2020, 24(11): 6470-6476.
10. Shao L, Meng D, Yang F, et al. Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells. Biochem Biophys Res Commun, 2017, 487(2): 194-200.
11. Tsuchiya Y, Ando D, Goto K, et al. High-intensity exercise causes greater irisin response compared with low-intensity exercise under similar energy consumption. Tohoku J Exp Med, 2014, 233(2): 135-140.
12. Zhang Y, Li R, Meng Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes, 2014, 63(2): 514-525.
13. Korta P, Pocheć E, Mazur-Biały A. Irisin as a multifunctional protein: implications for health and certain diseases. Medicina (Kaunas), 2019, 55(8): 485.
14. Daudon M, Bigot Y, Dupont J, et al. Irisin and the fibronectin type Ⅲ domain-containing family: structure, signaling and role in female reproduction. Reproduction, 2022, 164(1): R1-R9.
15. Zhao R. Irisin at the crossroads of inter-organ communications: challenge and implications. Front Endocrinol (Lausanne), 2022, 13: 989135.
16. Matsuo Y, Gleitsmann K, Mangner N, et al. Fibronectin type Ⅲ domain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines. J Cachexia Sarcopenia Muscle, 2015, 6(1): 62-72.
17. Kurdiova T, Balaz M, Vician M, et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol, 2014, 592(5): 1091-1107.
18. Luo Y, Qiao X, Xu L, et al. Irisin: circulating levels in serum and its relation to gonadal axis. Endocrine, 2022, 75(3): 663-671.
19. Lee HJ, Lee JO, Kim N, et al. Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK. Mol Endocrinol, 2015, 29(6): 873-881.
20. Luna-Ceron E, González-Gil AM, Elizondo-Montemayor L. Current insights on the role of irisin in endothelial dysfunction. Curr Vasc Pharmacol, 2022, 20(3): 205-220.
21. Zheng S, Chen N, Kang X, et al. Irisin alleviates FFA induced β-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway. Endocrine, 2022, 75(3): 740-751.
22. 毛楠, 周琬秋, 任思冲, 等. 鸢尾素与急性肾损伤的相关性研究. 成都医学院学报, 2022, 17(2): 174-179.
23. Sadeghi Shad J, Akbari R, Qujeq D, et al. Measurement of serum irisin in the different stages of chronic kidney disease. Caspian J Intern Med, 2019, 10(3): 314-319.
24. Csiky B, Sági B, Emmert V, et al. Cardiometabolic effects of irisin in patients with end-stage renal disease on regular hemo- or peritoneal dialysis. Blood Purif, 2022, 51(5): 450-457.
25. 邵雯, 李荣山, 周晓霜. 维持性血液透析合并肌少症患者血清鸢尾素的变化. 华西医学, 2020, 35(7): 788-793.
26. Arcidiacono T, Magni G, Macrina L, et al. Serum irisin may predict cardiovascular events in elderly patients with chronic kidney disease stage 3-5. J Ren Nutr, 2022, 32(3): 282-291.
27. Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev, 2015, 4(2): 20-27.
28. Bi J, Yang L, Wang T, et al. Irisin improves autophagy of aged hepatocytes via increasing telomerase activity in liver injury. Oxid Med Cell Longev, 2020, 2020: 6946037.
29. Zhang J, Bi J, Ren Y, et al. Involvement of GPX4 in irisin’s protection against ischemia reperfusion-induced acute kidney injury. J Cell Physiol, 2021, 236(2): 931-945.
30. Qiongyue Z, Xin Y, Meng P, et al. Post-treatment with irisin attenuates acute kidney injury in sepsis mice through anti-ferroptosis via the SIRT1/Nrf2 pathway. Front Pharmacol, 2022, 13: 857067.
31. Jin Z, Guo P, Li X, et al. Neuroprotective effects of irisin against cerebral ischemia/reperfusion injury via Notch signaling pathway. Biomed Pharmacother, 2019, 120: 109452.
32. Zhang R, Ji J, Zhou X, et al. Irisin pretreatment protects kidneys against acute kidney injury induced by ischemia/reperfusion via upregulating the expression of uncoupling protein 2. Biomed Res Int, 2020, 2020: 6537371.
33. Fan H, Su BJ, Le JW, et al. Salidroside protects acute kidney injury in septic rats by inhibiting inflammation and apoptosis. Drug Des Devel Ther, 2022, 16: 899-907.
34. Baisantry A, Berkenkamp B, Rong S, et al. Time-dependent p53 inhibition determines senescence attenuation and long-term outcome after renal ischemia-reperfusion. Am J Physiol Renal Physiol, 2019, 316(6): F1124-F1132.
35. Friederich M, Fasching A, Hansell P, et al. Diabetes-induced up-regulation of uncoupling protein-2 results in increased mitochondrial uncoupling in kidney proximal tubular cells. Biochim Biophys Acta, 2008, 1777(7/8): 935-940.
36. Zhou Y, Cai T, Xu J, et al. UCP2 attenuates apoptosis of tubular epithelial cells in renal ischemia-reperfusion injury. Am J Physiol Renal Physiol, 2017, 313(4): F926-F937.
37. Gwon DH, Hwang TW, Ro JY, et al. High endogenous accumulation of ω-3 polyunsaturated fatty acids protect against ischemia-reperfusion renal injury through AMPK-mediated autophagy in fat-1 mice. Int J Mol Sci, 2017, 18(10): 2081.
38. Formigari GP, Dátilo MN, Vareda B, et al. Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy. Sci Rep, 2022, 12(1): 9062.
39. Zunner BEM, Wachsmuth NB, Eckstein ML, et al. Myokines and resistance training: a narrative review. Int J Mol Sci, 2022, 23(7): 3501.
40. Wu F, Li Z, Cai M, et al. Aerobic exercise alleviates oxidative stress-induced apoptosis in kidneys of myocardial infarction mice by inhibiting ALCAT1 and activating FNDC5/irisin signaling pathway. Free Radic Biol Med. 2020, 158: 171-180.
41. Ortega-Lozano AJ, Jiménez-Uribe AP, Aranda-Rivera AK, et al. Expression profiles of kidney mitochondrial proteome during the progression of the unilateral ureteral obstruction: focus on energy metabolism adaptions. Metabolites, 2022, 12(10): 936.
42. Peng H, Wang Q, Lou T, et al. Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys. Nat Commun, 2017, 8(1): 1493.

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